2-Fluorobenzhydrazide → Toluene-4-sulfonic Acid 7-(2-Fluorophenyl)pyrazolo[1,5-d][1,2,4]triazin-2-yl Ester

HRID 1016396Notes

Reaction equation

HRID 1016396 reaction equation
O[CH2:2][C:3]1[NH:7][N:6]=[C:5]([O:8][S:9]([C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=2)(=[O:11])=[O:10])[CH:4]=1.[F:19][C:20]1[CH:29]=[CH:28][CH:27]=[CH:26][C:21]=1[C:22]([NH:24][NH2:25])=O>C(Cl)(Cl)Cl.C1(C)C(C)=CC=CC=1.[O-2].[O-2].[Mn+4]>[F:19][C:20]1[CH:29]=[CH:28][CH:27]=[CH:26][C:21]=1[C:22]1[N:7]2[N:6]=[C:5]([O:8][S:9]([C:12]3[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=3)(=[O:11])=[O:10])[CH:4]=[C:3]2[CH:2]=[N:25][N:24]=1

Participants

6

Reactant 2

HCID 1362882-FluorobenzhydrazideHCID 874174943-(Hydroxymethyl)-1H-pyrazol-5-yl 4-methylbenzenesulfonate

Product 1

HCID 87798670Toluene-4-sulfonic Acid 7-(2-Fluorophenyl)pyrazolo[1,5-d][1,2,4]triazin-2-yl EsterYield 94%

Reagents, catalysts & solvents 3

HCID 178418406HCID 178418406, compoundCatalystHCID 6212ChloroformSolventHCID 7237O-XyleneSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of toluene-4-sulfonic acid 5-hydroxymethyl-1H-pyrazol-3-yl ester (25 g, 93 mmol) in chloroform (800 ml) was added manganese dioxide (40.3 g, 465 mmol) and the suspension was heated at 70° C. for 14 h. The reaction mixture was filtered through sand/silica and the plug of silica was then washed several times with 10% methanol/dichloromethane. The combined filtrates were concentrated under vacuum to give crude aldehyde (25 g). Some of the crude aldehyde (2 g, 7.6 mmol) and 2-fluorobenzoic hydrazide (1.16 g, 7.6 mmol) were suspended in xylene (60 ml) and heated together at reflux for 3 h. After cooling, the solid formed was collected by filtration and dried under vacuum at 80° C. to afford 2.7 g (94%) of the condensation product as a light brown solid. Some of this condensation product, which existed in nmr solution as a mixture of isomers (1 g, 2.5 mmol), was dissolved in Dowtherm A (100 ml) and heated at 180° C. for 72 h. The whole reaction solution was cooled and eluted through a silica gel column using 0 to 15% ethyl acetate/dichloromethane to give the title compound as a light tan solid (0.614 g, 64%); 1H NMR (360 MHz, CDCl3) δ 2.46 (3H, s), 6.73 (1H, s), 7.18-7.35 (4H, m), 7.61 (1H, m), 7.71 (1H, m), 7.82 (2H, d, J 8.3 Hz), 9.33 (1H, s).

Workup

  1. filtrationThe reaction mixture was filtered through sand/silica
  2. washthe plug of silica was then washed several times with 10% methanol/dichloromethane
  3. concentrationThe combined filtrates were concentrated under vacuum
  4. customto give crude aldehyde (25 g)
  5. temperatureheated together
  6. temperatureat reflux for 3 h
  7. temperatureAfter cooling
  8. customthe solid formed
  9. filtrationwas collected by filtration
  10. customdried under vacuum at 80° C.

Sources & evidence

ORD record
ord-7dd654bcccb4415899edd75c50dfb79f
Source dataset
uspto-grants-2002_11
Patent number
US06476030B1

Reaction notes

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